Lipid-dependent regulation of human Th17 cell function
人类 Th17 细胞功能的脂质依赖性调节
基本信息
- 批准号:9176733
- 负责人:
- 金额:$ 44.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-01 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsArthritisAutoimmune DiseasesAutoimmune ProcessBiogenesisCD4 Positive T LymphocytesCell Differentiation processCell LineageCell physiologyCellsChemicalsColitisCytoplasmDataDevelopmentDiseaseDisease modelEffector CellFamilyFatty AcidsFatty LiverGene ExpressionGene TargetingGenesGenetic ScreeningGenetic screening methodGoalsHelper-Inducer T-LymphocyteHumanImmuneInflammationInflammatoryInflammatory Bowel DiseasesInterleukin-17KineticsLeadLigandsLightLinkLipidsLiver diseasesMemoryMetabolicMetabolismModelingMolecularMultiple SclerosisMusNonesterified Fatty AcidsNuclear Hormone ReceptorsOrganellesOrphanPPAR gammaPathologyPathway interactionsPhysiologicalPlayPolyunsaturated Fatty AcidsProductionProteinsPsoriasisRegulationRegulatory T-LymphocyteRetinoidsRoleSpecificitySterolsT cell differentiationT-LymphocyteTestingTriglyceridesabstractingchemical geneticscytokinegain of functionknock-downlipid metabolismmacromoleculenovelnovel therapeuticsprogramsreceptorresponsesmall hairpin RNAsmall moleculetreatment strategy
项目摘要
Abstract
Th17 cells are an Interleukin-17-producing subset of CD4+ T effector cells that are centrally
implicated in many human inflammatory and autoimmune diseases, from inflammatory bowel
disease to multiple sclerosis. The retinoid orphan receptor gamma t (RORγt), a nuclear hormone
receptor, programs Th17 cell development and function. With the ultimate goal of modulating
inflammatory T cells in disease settings, we undertook chemical and genetic screening to
identify RORγt target genes that drive human Th17 cell function. Intriguingly, our results
implicated a group of genes in a novel pathway that would link lipid metabolism, RORγt activity
and Th17 cell functions. We will thus test the hypothesis that Th17 cell function is controlled in
large part, by RORγt target genes, via lipid droplets (LDs) (cellular organelles associated with
lipid metabolism). We will take the following approaches: First, we will determine if LD- related
genes – specifically, HILPDA and BNIP3 – are necessary, sufficient and specific regulators of
human Th17 cell functions. Second, we will elucidate the molecular mechanisms by which LDs
modulate Th17 cell differentiation. Third, using autoimmune disease models in mice, we will
determine the physiological significance of LDs in inflammation and autoimmune pathologies.
Our results may shed a light on novel lipid-regulatory mechanisms that control Th17 cell
responses in inflammatory diseases.
摘要
Th 17细胞是产生白细胞介素-17的CD 4 + T效应细胞亚群,其集中在
与许多人类炎症性和自身免疫性疾病有关,
多发性硬化症类维生素A孤儿受体γ t(RORγt),一种核激素
受体,程序Th 17细胞的发育和功能。最终目的是调节
在疾病环境中的炎性T细胞,我们进行了化学和遗传筛查,
鉴定驱动人Th 17细胞功能RORγt靶基因。有趣的是,我们的结果
提示一组基因参与了一种新的途径,该途径将脂质代谢、RORγt活性
Th 17细胞功能因此,我们将检验Th 17细胞功能在以下条件下受控制的假设:
很大一部分是通过RORγt靶基因,通过脂滴(LDs)(与RORγ t相关的细胞器),
脂质代谢)。我们将采取以下方法:首先,我们将确定是否与LD相关
基因-特别是,HILPDA和BNIP 3-是必要的,足够的和特定的调节剂,
人Th 17细胞功能其次,我们将阐明LD的分子机制,
调节Th 17细胞分化。第三,使用小鼠自身免疫性疾病模型,我们将
确定LD在炎症和自身免疫病理学中的生理学意义。
我们的研究结果可能揭示新的脂质调控机制,控制Th 17细胞
炎症性疾病的反应。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jun R. Huh其他文献
Brain-wide mapping of immune receptors uncovers a neuromodulatory role of IL-17E and the receptor IL-17RB
大脑范围内免疫受体的图谱揭示了 IL-17E 及其受体 IL-17RB 的神经调节作用
- DOI:
10.1016/j.cell.2025.03.006 - 发表时间:
2025-04-17 - 期刊:
- 影响因子:42.500
- 作者:
Yunjin Lee;Tomoe Ishikawa;Hyeseung Lee;Byeongjun Lee;Changhyeon Ryu;Irene Davila Mejia;Minjin Kim;Guangqing Lu;Yujin Hong;Mengyang Feng;Hyeyoon Shin;Sylvain Meloche;Richard M. Locksley;Ekaterina Koltsova;Sergei I. Grivennikov;Myriam Heiman;Gloria B. Choi;Jun R. Huh - 通讯作者:
Jun R. Huh
Apoptosis: Sculpture of a fly's head
细胞凋亡:苍蝇头部雕塑
- DOI:
10.1038/418926a - 发表时间:
2002 - 期刊:
- 影响因子:64.8
- 作者:
Jun R. Huh;B. Hay - 通讯作者:
B. Hay
Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4sup+/sup T cells
母体肠道细菌通过改变 CD4+T 细胞的染色质景观,在患有神经发育障碍的后代中驱动肠道炎症。
- DOI:
10.1016/j.immuni.2021.11.005 - 发表时间:
2022-01-11 - 期刊:
- 影响因子:26.300
- 作者:
Eunha Kim;Donggi Paik;Ricardo N. Ramirez;Delaney G. Biggs;Youngjun Park;Ho-Keun Kwon;Gloria B. Choi;Jun R. Huh - 通讯作者:
Jun R. Huh
Gut-innervating nociceptor neurons protect against enteric infection by modulating the microbiota and Peyer’s patch microfold cells
肠道神经伤害感受器神经元通过调节微生物群和派尔氏集结微褶皱细胞来防止肠道感染
- DOI:
10.1101/580555 - 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
N. Lai;Melissa A. Musser;Felipe A. Pinho;P. Baral;Pingchuan Ma;D. Potts;Zuojia Chen;Donggi Paik;Salima Soualhi;Hailian Shi;Aditya Misra;Kaitlin Goldstein;K. Sivanathan;A. Jacobson;Antonia Wallrapp;Valentina N. Lagomarsino;V. Kuchroo;Roni Nowarski;M. Starnbach;N. Surana;Dingding An;Chuan Wu;Jun R. Huh;M. Rao;I. Chiu - 通讯作者:
I. Chiu
Inflammatory and anti-inflammatory cytokines bidirectionally modulate amygdala circuits regulating anxiety
炎症细胞因子和抗炎细胞因子双向调节调节焦虑的杏仁核回路
- DOI:
10.1016/j.cell.2025.03.005 - 发表时间:
2025-04-17 - 期刊:
- 影响因子:42.500
- 作者:
Byeongjun Lee;Jeong-Tae Kwon;Yire Jeong;Hannah Caris;Dongsun Oh;Mengyang Feng;Irene Davila Mejia;Xiaoying Zhang;Tomoe Ishikawa;Brianna R. Watson;Jeffrey R. Moffitt;Kwanghun Chung;Jun R. Huh;Gloria B. Choi - 通讯作者:
Gloria B. Choi
Jun R. Huh的其他文献
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{{ truncateString('Jun R. Huh', 18)}}的其他基金
Dissecting the modulatory functions of interleukin-17 in Alzheimer's Disease
剖析 IL-17 在阿尔茨海默病中的调节功能
- 批准号:
10590495 - 财政年份:2022
- 资助金额:
$ 44.27万 - 项目类别:
Pregnancy influences maternal immune cell function and fetal brain development
怀孕影响母体免疫细胞功能和胎儿大脑发育
- 批准号:
10669604 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Pregnancy influences maternal immune cell function and fetal brain development
怀孕影响母体免疫细胞功能和胎儿大脑发育
- 批准号:
10011840 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Pregnancy influences maternal immune cell function and fetal brain development
怀孕影响母体免疫细胞功能和胎儿大脑发育
- 批准号:
10437718 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Pregnancy influences maternal immune cell function and fetal brain development
怀孕影响母体免疫细胞功能和胎儿大脑发育
- 批准号:
10215459 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Bacterial metabolites controlling Th17 cells
控制 Th17 细胞的细菌代谢物
- 批准号:
9571441 - 财政年份:2016
- 资助金额:
$ 44.27万 - 项目类别:
Lipid-dependent regulation of human Th17 cell function
人类 Th17 细胞功能的脂质依赖性调节
- 批准号:
9316588 - 财政年份:2016
- 资助金额:
$ 44.27万 - 项目类别:
Lipid-dependent regulation of human Th17 cell function
人类 Th17 细胞功能的脂质依赖性调节
- 批准号:
9582212 - 财政年份:2016
- 资助金额:
$ 44.27万 - 项目类别:
Bacterial metabolites controlling Th17 and Treg cells
控制 Th17 和 Treg 细胞的细菌代谢物
- 批准号:
10670406 - 财政年份:2016
- 资助金额:
$ 44.27万 - 项目类别:
Bacterial metabolites controlling Th17 and Treg cells
控制 Th17 和 Treg 细胞的细菌代谢物
- 批准号:
10365478 - 财政年份:2016
- 资助金额:
$ 44.27万 - 项目类别:
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